L-Glutamic acid, N-coco acyl derivs., compds. with triethanolamine (1:1)

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

Introduction

L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1) [EC Number: 269-084-6, CAS Number: 68187-29-1] is a UVCB substance. Physico-chemical properties of L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1), together with QSAR assessments and the results of in vitro and in vivo studies that were conducted either with the substance or with related, read-across substances have been used to determine, as far as possible, a toxicokinetic profile for L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1).

Physicochemical properties

L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1) is a UVCB. It is a white to pale yellow solid (a “sticky paste”) at room temperature with a melting point in the region of 131-134°C. Its relative density and vapour pressure at 20°C are 0.97 and 0.012 Pa, respectively. The partition coefficient (log Kow/Pow, 25°C) for each constituent ranged from -3.5809 to 0.3479 and for chemical safety assessment a weighted average log Pow of -1.58 was assigned. It is soluble in water at 383 mg/mL at 20°C.

Absorption

Oral absorption

The oral LD₅₀of L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1) is reported to be 6500 mg/kg bw, with mortality observed at dose levels of 4.8 -14.3 g/kg (100% mortality at 8.3 g/kg and above). The study is of limited reliability and provides no further information for determining oral absorption. Data from an acute oral toxicity study on TEA Lauroyl L-Glutamate Solution (LT-12), a related substance that has been proposed for read-across purposes, indicates an LD₅₀of >5000 mg/kg bw but < 10,000 mg/kg bw and at lethal dose levels clinical signs included cyanosis, opisthotonus and convulsions. 

The available in vivo data, indicate that oral absorption of the read across substance TEA Lauroyl L-Glutamate Solution (LT-12) does occur and therefore absorption of L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1) is also expected. L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1) is water soluble and would be expected to dissolve readily in gastrointestinal fluid. Furthermore, it has a moderate log Pow (average log Pow -1.58), which would favour absorption by passive diffusion. The substance is a UVCB and with the data available, it is not possible to determine if all components would be absorbed to the same degree. Therefore, in the absence of any other information and for the purposes of human DNEL setting, 50% oral absorption is assumed for human health risk assessment purposes.

Dermal absorption

No data are available regarding the dermal absorption of L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1). Although the substance was concluded to be non-corrosive and non-irritating to skin inin vitrostudies using a 3D skin model, both studies showed a reduction in keratinocyte viability compared to controls, suggesting some penetration of the dermal layer had occurred. In addition, a 5% solution of L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1) was concluded to be slightly irritating in an in vivo skin irritation study in rabbits; skin irritation is known to enhance penetration.

The available data, indicate that some degree of dermal absorption of L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1) may occur. This is supported by its high water solubility and the moderate lipophilic nature of at least some of its constituents. However, several components have log Pow values below -1, which would limit their potential to cross the stratum corneum. Therefore, in the absence of any other information and for the purposes of human DNEL setting, 10% dermal absorption (based on the ECHA guidance) is assumed for human health risk assessment purposes.

Inhalation absorption

No data are available on acute inhalation toxicity of either the substance or any read across substance. 

 

L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1) iswater soluble with a moderate log P value (for at least some of the constituents); this would favour absorptiondirectly across the respiratory tract epithelium by passive diffusion.Therefore, in the absence of any other information and for the purposes of human DNEL setting, 100% inhalation absorption is assumed for human health risk assessment purposes.

Distribution, Metabolism and Elimination

No in vivo information is available to describe the distribution, metabolism or elimination ofL-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1). However, given its organic nature, it is expected that once absorbed the components of the substance will be widely distributed within the body and metabolised to substrates of endogenous metabolism or excreted mainly unchanged (triethanolamine). The acyl residues will be distributed via chylomicrons, while glutamic acid will reach the liver, and there subjected to metabolism or re-used for other metabolic processes.

The acyl residues and glutamate will be used as a source of energy within the citric acid cycle; in case of glutamate, it will be also used for the synthesis of peptides or other amino acids, or excreted in the form of urea.

Most of the components deriving from metabolism/degradation of the parent compound will be re-used for other metabolic processes within the body and eventually excreted in the urine. Based on ADME data in rats, most of the released triethanolamine is expected to be excreted unchanged, with only a minor part (<3%) as glucuronide conjugates. Excretion will be via both urine and faeces.

Bioaccumulation is considered unlikely to occur.

Conclusions

Based on in vitro and in vivo data from studies performed with L-Glutamic acid, N-coco acyl derivative, compounds with triethanolamine (1:1), oral absorption is estimated at 50%, inhalation absorption is estimated at 100% and dermal absorption is estimated at 10%.

There is no potential for bioaccumulation.